Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Investigational New Drug Applications, 3462-3467 [2019-01962]
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Federal Register / Vol. 84, No. 29 / Tuesday, February 12, 2019 / Notices
Safety Labeling Changes—
Implementation of Section 505(o)(4) of
the Federal Food, Drug, and Cosmetic
Act
OMB Control Number 0910–0734—
Extension
Section 505(o)(4) of the FD&C Act (21
U.S.C. 355(o)(4)) authorizes FDA to
require and, if necessary, order labeling
changes if FDA becomes aware of new
safety information that it believes
should be included in the labeling of
certain prescription drug and biological
products approved under section 505 of
the FD&C Act or section 351 of the
Public Health Service Act (PHS Act) (42
U.S.C. 262). Section 505(o)(4) of the
FD&C Act applies to prescription drug
products with an approved new drug
application (NDA) under section 505(b)
of the FD&C Act, biological products
with an approved biologics license
application under section 351 of the
PHS Act, or prescription drug products
with an approved abbreviated new drug
application under section 505(j) of the
FD&C Act if the reference listed drug
with an approved NDA is not currently
marketed. Section 505(o)(4) imposes
time frames for application holders to
submit, and FDA staff to review, such
changes and gives FDA enforcement
tools to bring about timely and
appropriate labeling changes. To
implement these provisions we
developed the guidance entitled
‘‘Guidance for Industry: Safety Labeling
Changes—Implementation of Section
505(o)(4) of the Federal Food, Drug, and
Cosmetic Act,’’ which provides
instruction on: (1) A description of the
types of safety labeling changes that
ordinarily might be required; (2) how
FDA plans to determine what
constitutes new safety information; (3)
the procedures involved in requiring
safety labeling changes, and (4)
enforcement of the requirements for
safety labeling changes. The guidance is
available on our website at https://
www.fda.gov/downloads/drugs/
guidancecomplianceregulatory
information/guidances/ucm250783.pdf.
FDA requires safety labeling changes
by sending a notification letter to the
application holder. Under section
505(o)(4)(B) of the FD&C Act, the
application holder must respond to
FDA’s notification by submitting a
labeling supplement or notifying FDA
that the applicant does not believe the
labeling change is warranted and by
submitting a statement detailing why
the application holder does not believe
a change is warranted (a rebuttal
statement).
Based on our experience to date with
safety labeling changes requirements
under section 505(o)(4) of the FD&C Act,
we estimate that approximately 36
application holders will elect to submit
approximately 1 rebuttal statement each
year and that each rebuttal statement
will take approximately 6 hours to
prepare.
In addition, the guidance explains
that labeling prepared in response to a
safety labeling change notification
should be available on the application
holder’s website within 10 calendar
days of approval. We estimate that
approximately 351 application holders
will post new labeling one time each
year in response to a safety labeling
change notification and that the posting
of the labeling will take approximately
4 hours to prepare.
We estimate the burden of the
information collection as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1
Activity
Number of
respondents
Number of
responses per
respondent
Total annual
responses
Average
burden per
response
Total hours
Rebuttal statement ...............................................................
36
1
36
6
216
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
Type of submission
Number of
respondents
Number of
disclosures
per
respondent
Total annual
disclosures
Average
burden per
disclosure
Total hours
Posting approved labeling on application holder’s website
351
1
351
4
1,404
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
We have adjusted our estimated
annual number of respondents
downward by 62 since the last OMB
approval of the information collection.
The decrease reflects that we have
issued fewer safety labeling
notifications, and thus fewer postings
are required and fewer rebuttals are
expected.
Dated: February 6, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019–01918 Filed 2–11–19; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2014–N–1721]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Investigational
New Drug Applications
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a proposed collection of
SUMMARY:
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information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
DATES: Fax written comments on the
collection of information by March 14,
2019.
ADDRESSES: To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, Fax: 202–
395–7285, or emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0014. Also
include the FDA docket number found
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Federal Register / Vol. 84, No. 29 / Tuesday, February 12, 2019 / Notices
in brackets in the heading of this
document.
FOR FURTHER INFORMATION CONTACT:
JonnaLynn Capezzuto, Office of
Operations, Food and Drug
Administration, Three White Flint
North, 10A–12M, 11601 Landsdown St.,
North Bethesda, MD 20852, 301–796–
3794, PRAStaff@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
Investigational New Drug
Application—21 CFR Part 312
OMB Control Number 0910–0014–
Extension
This information collection supports
FDA regulations in 21 CFR part 312
covering Investigational New Drugs.
Part 312 implements provisions of
section 505(i) of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) (21 U.S.C.
355(i)) requiring FDA to issue
regulations under which the clinical
investigation of the safety and
effectiveness of unapproved new drugs
and biological products can be
conducted.
FDA is charged with implementing
statutory requirements that ensure drug
products marketed in the United States
are shown to be safe and effective,
properly manufactured, and properly
labeled for their intended uses. Section
505(a) of the FD&C Act provides that a
new drug may not be introduced or
delivered for introduction into interstate
commerce in the United States unless
FDA has previously approved a new
drug application (NDA). FDA approves
an NDA only if the sponsor of the
application first demonstrates that the
drug is safe and effective for the
conditions prescribed, recommended, or
suggested in the product’s labeling.
Proof must consist, in part, of adequate
and well-controlled studies, including
studies in humans, that are conducted
by qualified experts.
The investigational new drug
application (IND) regulations under part
312 establish reporting requirements
that include an initial application as
well as amendments to that application,
reports on significant revisions of
clinical investigation plans, and
information on a drug’s safety or
effectiveness. In addition, the sponsor is
required to give FDA an annual
summary of the previous year’s clinical
experience. The regulations also include
recordkeeping requirements pertaining
to the disposition of drugs, records
pertaining to individual case histories,
and certain other documentation
verifying the fulfillment of
responsibilities by clinical investigators.
Submissions are reviewed by medical
officers and other Agency scientific
reviewers assigned responsibility for
overseeing a specific study. The details
and complexity of these requirements
are dictated by the scientific procedures
and human subject safeguards that must
be followed in the clinical tests of
investigational new drugs.
The IND information collection
requirements provide the means by
which FDA can monitor the clinical
investigation of the safety and
effectiveness of unapproved new drugs
and biological products, including the
following: (1) Monitor the safety of
ongoing clinical investigations; (2)
determine whether the clinical testing of
a drug should be authorized; (3) ensure
production of reliable data on the
metabolism and pharmacological action
of the drug in humans; (4) obtain timely
information on adverse reactions to the
drug; (5) obtain information on side
effects associated with increasing doses;
(6) obtain information on the drug’s
effectiveness; (7) ensure the design of
well-controlled, scientifically valid
studies; and (8) obtain other information
pertinent to determining whether
clinical testing should be continued and
information related to the protection of
human subjects. Without the
information provided by industry as
required under the IND regulations,
FDA cannot authorize or monitor the
clinical investigations that must be
conducted before authorizing the sale
and general use of new drugs. These
reports enable FDA to monitor a study’s
progress, to ensure the safety of subjects,
to ensure that a study will be conducted
ethically, and to increase the likelihood
that the sponsor will conduct studies
that will be useful in determining
whether the drug should be marketed
and available for use in medical
practice.
To assist respondents with certain
reporting requirements under part 312,
we have developed two forms: Form
FDA 1571 entitled, ‘‘Investigational
New Drug Application (IND)’’ and Form
FDA 1572 entitled, ‘‘Statement of
Investigator.’’ Anyone who intends to
conduct a clinical investigation must
submit Form FDA 1571 as instructed.
The reporting elements include: (1) A
cover sheet containing background
information on the sponsor and
investigator; (2) a table of contents; (3)
an introductory statement and general
investigational plan; (4) an investigator’s
brochure describing the drug substance;
(5) a protocol for each planned study;
(6) chemistry, manufacturing, and
control information for each
investigation; (7) pharmacology and
toxicology information for each
investigation; and (8) previous human
experience with the investigational
drug. Form FDA 1572 is executed and
submitted by the IND sponsor before an
investigator may participate in an
investigation. It includes background
information on the investigator as well
as the investigation, and a general
outline of the planned investigation and
study protocol.
In the Federal Register of October 4,
2018 (83 FR 50102) FDA published a 60day notice requesting public comment
on the proposed collection of
information. We received one comment.
The comment did not pertain to the
regulations or estimates provided in the
60-day notice requesting that OMB
extend its approval for the information
collection in these regulations. Rather,
the comment discussed issues that
pertained to Docket No. FDA–2010–D–
0503 for the ‘‘Guidance for Clinical
Investigators, Sponsors, and
Institutional Review Boards (IRBs):
Investigational New Drug Applications
(INDs)—Determining Whether Human
Research Studies Can Be Conducted
Without an IND.’’ Accordingly, we have
submitted the comment to Docket No.
FDA–2010–D–0503.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN FOR HUMAN DRUGS (CDER) 1
Number of
respondents
21 CFR section
§ 312.2(e); Requests for FDA advice on the applicability of
part 312 to a planned clinical investigation ......................
§ 312.8; Requests to charge for an investigational drug .....
§ 312.10; Requests to waive a requirement in part 312 .....
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Number of
responses per
respondent
400
74
86
Fmt 4703
Sfmt 4703
Total annual
responses
1
1.23
1.84
E:\FR\FM\12FEN1.SGM
400
91
158
12FEN1
Average
burden per
response
24
48
24
Total hours
9,600
4,368
3,792
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TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN FOR HUMAN DRUGS (CDER) 1—Continued
§ 312.23(a) through (f); IND content and format (including
Form FDA 1571) ..............................................................
§ 312.30(a) through (e); Protocol amendments ...................
§ 312.31(b); Information amendments .................................
§ 312.32(c) and (d); IND safety reports ...............................
§ 312.33(a) through (f); IND annual reports ........................
§ 312.38(b) and (c); Notifications of withdrawal of an IND ..
§ 312.42; Sponsor requests that a clinical hold be removed, including sponsor submission of a complete response to the issues identified in the clinical hold order
§ 312.44(c) and (d); Sponsor responses to FDA when IND
is terminated .....................................................................
§ 312.45(a) and (b); Sponsor requests for or responses to
an inactive status determination of an IND by FDA ........
§ 312.47; Meetings, including ‘‘End-of-Phase 2’’ meetings
and ‘‘Pre-NDA’’ meetings .................................................
§ 312.54(a); Sponsor submissions to FDA concerning investigations involving an exception from informed consent under § 50.24 ............................................................
§ 312.54(b); Sponsor notifications to FDA and others concerning an IRB determination that it cannot approve research because it does not meet the criteria in the exception from informed consent in § 50.24(a) ...................
§ 312.56(b), (c), and (d); Sponsor notifications to FDA and
others resulting from: (1) The sponsor’s monitoring of all
clinical investigations and determining that an investigator is not in compliance with the investigation agreements; (2) the sponsor’s review and evaluation of the
evidence relating to the safety and effectiveness of the
investigational drug; and (3) the sponsor’s determination
that the investigational drug presents an unreasonable
and significant risk to subjects .........................................
§ 312.58(a); Sponsor’s submissions of clinical investigation
records to FDA on request during FDA inspections ........
§ 312.70; During the disqualification process of a clinical
investigator by FDA, the number of investigator responses or requests to FDA following FDA’s notification
to an investigator of its failure to comply with investigation requirements ..............................................................
§ 312.110(b)(4) and (b)(5); Written certifications and written statements submitted to FDA relating to the export
of an investigational drug .................................................
§ 312.120(b); Submissions to FDA of ‘‘supporting information’’ related to the use of foreign clinical studies not
conducted under an IND ..................................................
§ 312.120(c); Waiver requests submitted to FDA related to
the use of foreign clinical studies not conducted under
an IND ..............................................................................
§ 312.130; Requests for disclosable information in an IND
and for investigations involving an exception from informed consent under § 50.24 .........................................
§§ 312.310(b) and 312.305(b); Submissions related to expanded access and treatment of an individual patient ....
§ 312.310(d); Submissions related to emergency use of an
investigational new drug ...................................................
§§ 312.315(c) and 312.305(b); Submissions related to expanded access and treatment of an intermediate-size
patient population .............................................................
§ 312.320(b); Submissions related to a treatment IND or
treatment protocol ............................................................
Total ..............................................................................
1 There
Number of
responses per
respondent
Number of
respondents
21 CFR section
Average
burden per
response
Total annual
responses
2,187
4,418
6,691
867
3,376
930
1.7
5.52
3.32
15.78
2.86
1.61
3,718
24,387
22,214
13,681
9,655
1,497
1,600
284
100
32
360
28
5,948,800
6,925,908
2,221,400
437,792
3,475,800
41,916
198
1.38
273
284
77,532
12
1.16
14
16
224
231
1.84
425
12
5,100
122
1.51
184
160
29,440
15
2.4
36
48
1,728
2
1
2
48
96
6,100
7
42,700
80
3,416,000
73
1
73
8
584
4
1
4
40
160
11
26.28
289
75
21,675
1,414
8.62
12,189
32
390,048
35
2.34
82
24
1,968
3
1
3
8
24
935
2.77
2,590
8
20,720
480
2.15
1,032
16
16,512
118
2.52
297
120
35,640
10
12.9
129
300
38,700
........................
........................
........................
........................
23,125,527
are no capital costs or operating and maintenance costs associated with this collection of information.
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TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR HUMAN DRUGS (CDER) 1
Number of
recordkeepers
21 CFR section
§ 312.52(a); Sponsor records for the transfer of obligations
to a contract research organization .................................
§ 312.57; Sponsor recordkeeping showing the receipt,
shipment, or other disposition of the investigational drug
and any financial interests ...............................................
§ 312.62(a); Investigator recordkeeping of the disposition
of drugs ............................................................................
§ 312.62(b); Investigator recordkeeping of case histories of
individuals .........................................................................
§ 312.160(a)(3); Records pertaining to the shipment of
drugs for investigational use in laboratory research animals or in vitro tests .........................................................
§ 312.160(c); Shipper records of alternative disposition of
unused drugs ....................................................................
Total ..............................................................................
Number of
records per
recordkeeper
Total annual
records
Average
burden per
recordkeeping
Total hours
1,300
1
1,300
2
2,600
13,000
1
13,000
100
1,300,000
13,000
1
13,000
40
520,000
13,000
1
13,000
40
520,000
547
1.43
782
* 0.50
391
547
1.43
782
* 0.50
391
........................
........................
........................
........................
2,343,382
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
* 30 minutes.
TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN FOR HUMAN DRUGS (CDER) 1
Number of
respondents
21 CFR section
§ 312.53(c); Investigator reports submitted to the sponsor,
including Form FDA 1572, curriculum vitae, clinical protocol, and financial disclosure ..........................................
§ 312.55(a); Investigator brochures submitted by the sponsor to each investigator ....................................................
§ 312.55(b); Sponsor reports to investigators on new observations, especially adverse reactions and safe use ...
§ 312.64; Investigator reports to the sponsor, including
progress reports, safety reports, final reports, and financial disclosure reports ......................................................
Total ..............................................................................
1 There
Number of
disclosures
per
respondent
Total annual
disclosures
Average
burden per
disclosure
Total hours
1,732
7.94
13,752
80
1,100,160
995
4
3,980
48
191,040
995
4
3,980
48
191,040
13,000
1
13,000
24
312,000
........................
........................
........................
........................
1,794,240
are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 4—ESTIMATED ANNUAL REPORTING BURDEN FOR BIOLOGICS (CBER) 1
Number of
respondents
21 CFR section
§ 312.2(e); Requests for FDA advice on the applicability of
part 312 to a planned clinical investigation ......................
§ 312.8; Requests to charge for an investigational drug .....
§ 312.10;Requests to waive a requirement in part 312 .......
§ 312.23(a) through (f); IND content and format .................
§ 312.30(a) through (e); Protocol amendments ...................
§ 312.31 (b); Information amendments ................................
§ 312.32(c) and (d); IND Safety reports ..............................
§ 312.33(a) through (f); IND Annual reports ........................
§ 312.38(b) and (c); Notifications of withdrawal of an IND ..
§ 312.42; Sponsor requests that a clinical hold be removed, including sponsor submission of a complete response to the issues identified in the clinical hold order
§ 312.44(c) and (d); Sponsor responses to FDA when IND
is terminated .....................................................................
§ 312.45(a) and (b); Sponsor requests for or responses to
an inactive status determination of an IND by FDA ........
§ 312.47; Meetings, including ‘‘End-of-Phase 2’’ meetings
and ‘‘Pre-NDA’’ meetings .................................................
§ 312.53(c); Investigator reports submitted to the sponsor,
including Form FDA 1572, curriculum vitae, clinical protocol, and financial disclosure ..........................................
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Number of
responses per
respondent
Total annual
responses
Average
burden per
response
Total hours
217
20
2
335
694
77
161
745
134
1.18
1.50
1
1.35
5.84
2.43
8.83
2.14
1.69
256
30
2
452
4,053
187
1,422
1,594
226
24
48
24
1,600
284
100
32
360
28
6,144
1,440
48
723,200
1,151,052
18,700
45,504
573,840
6,328
67
1.30
87
284
24,708
34
1.15
39
16
624
55
1.38
76
12
912
88
1.75
154
160
24,640
453
6.33
2,867
80
229,360
Sfmt 4703
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TABLE 4—ESTIMATED ANNUAL REPORTING BURDEN FOR BIOLOGICS (CBER) 1—Continued
§ 312.54(a); Sponsor submissions to FDA concerning investigations involving an exception from informed consent under § 50.24 ............................................................
§ 312.54(b); Sponsor notifications to FDA and others concerning an IRB determination that it cannot approve research because it does not meet the criteria in the exception from informed consent in § 50.24(a) ...................
§ 312.55(a); Number of investigator brochures submitted
by the sponsor to each investigator .................................
§ 312.55(b); Number of sponsor reports to investigators on
new observations, especially adverse reactions and safe
use ....................................................................................
§ 312.56(b), (c), and (d); Sponsor notifications to FDA and
others resulting from: (1) The sponsor’s monitoring of all
clinical investigations and determining that an investigator is not in compliance with the investigation agreements; (2) the sponsor’s review and evaluation of the
evidence relating to the safety and effectiveness of the
investigational drug; and (3) the sponsor’s determination
that the investigational drug presents an unreasonable
and significant risk to subjects .........................................
§ 312.58(a); Number of sponsor’s submissions of clinical
investigation records to FDA on request during FDA inspections ..........................................................................
§ 312.64; Number of investigator reports to the sponsor,
including progress reports, safety reports, final reports,
and financial disclosure reports .......................................
§ 312.70; During the disqualification process of a clinical
investigator by FDA, the number of investigator responses or requests to FDA following FDA’s notification
to an investigator of its failure to comply with investigation requirements ..............................................................
§ 312.110(b)(4) and (b)(5); Number of written certifications
and written statements submitted to FDA relating to the
export of an investigational drug ......................................
§ 312.120(b); Number of submissions to FDA of ‘‘supporting information’’ related to the use of foreign clinical
studies not conducted under an IND ...............................
§ 312.120(c); Number of waiver requests submitted to
FDA related to the use of foreign clinical studies not
conducted under an IND ..................................................
§ 312.130; Number of requests for disclosable information
in an IND and for investigations involving an exception
from informed consent under § 50.24 ..............................
§ 312.310(b) and 312.305(b); Number of submissions related to expanded access and treatment of an individual
patient ...............................................................................
§ 312.310(d);Number of submissions related to emergency
use of an investigational new drug ..................................
§ 312.315(c) and 312.305(b); Number of submissions related to expanded access and treatment of an intermediate-size patient population .......................................
§ 312.320(b); Number of submissions related to a treatment IND or treatment protocol .......................................
Total ..............................................................................
1 There
Number of
responses per
respondent
Number of
respondents
21 CFR section
Average
burden per
response
Total annual
responses
Total hours
1
1
1
48
48
1
1
1
48
48
239
1.91
456
48
21,888
243
4.95
1,203
48
57,744
108
2.21
239
80
19,120
7
1
7
8
56
2,728
3.82
10,421
24
250,104
5
1
5
40
200
18
1
18
75
1,350
280
9.82
2,750
32
88,000
7
2.29
16
24
384
350
1.34
469
8
3,752
78
1.08
84
8
672
76
2.76
210
16
3,360
9
1
9
120
1,080
1
1
1
300
300
........................
........................
........................
........................
3,254,606
are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 5—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR BIOLOGICS (CBER) 1
Number of
recordkeepers
21 CFR section
§ 312.52(a); Sponsor records for the transfer of obligations
to a contract research organization .................................
§ 312.57; Sponsor recordkeeping showing the receipt,
shipment, or other disposition of the investigational
drug, and any financial interests ......................................
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Number of
records per
recordkeeper
Total annual
records
Average
burden per
recordkeeping
Total hours
75
1.40
105
2
210
335
2.70
904
100
90,400
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TABLE 5—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR BIOLOGICS (CBER) 1—Continued
Number of
recordkeepers
21 CFR section
§ 312.62(a); Investigator recordkeeping of the disposition
of drugs ............................................................................
§ 312.62(b); Investigator recordkeeping of case histories of
individuals .........................................................................
§ 312.160(a)(3); Records pertaining to the shipment of
drugs for investigational use in laboratory research animals or in vitro tests .........................................................
§ 312.160(c); Shipper records of alternative disposition of
unused drugs ....................................................................
Total ..............................................................................
Number of
records per
recordkeeper
Total annual
records
Average
burden per
recordkeeping
Total hours
453
1
453
40
18,120
453
1
453
40
18,120
111
1.40
155
* 0.5
78
111
1.40
155
* 0.5
78
........................
........................
........................
........................
127,006
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
* 30 minutes.
Because we have received an
increased number of IND submissions
since the last OMB approval of the
information collection, we have
increased our estimate of the associated
burden accordingly.
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Dated: February 6, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
Hospira, Inc., et al.; Withdrawal of
Approval of 12 Abbreviated New Drug
Applications
[FR Doc. 2019–01962 Filed 2–11–19; 8:45 am]
AGENCY:
BILLING CODE 4164–01–P
Food and Drug Administration
[Docket No. FDA–2019–N–0163]
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or Agency) is
withdrawing approval of 12 abbreviated
new drug applications (ANDAs) from
multiple applicants. The applicants
notified the Agency in writing that the
drug products were no longer marketed
and requested that the approval of the
applications be withdrawn.
SUMMARY:
Approval is withdrawn as of
March 14, 2019.
FOR FURTHER INFORMATION CONTACT:
Trang Tran, Center for Drug Evaluation
and Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 75, Rm. 1671, Silver Spring,
MD 20993–0002, 240–402–7945,
Trang.Tran@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: The
applicants listed in the table have
informed FDA that these drug products
are no longer marketed and have
requested that FDA withdraw approval
of the applications under the process
described in § 314.150(c) (21 CFR
314.150(c)). The applicants have also,
by their requests, waived their
opportunity for a hearing. Withdrawal
of approval of an application or
abbreviated application under
§ 314.150(c) is without prejudice to
refiling.
DATES:
Application No.
Drug
Applicant
ANDA 065343 .............................
Hospira, Inc., 275 North Field Dr., Bldg. H1, Lake
Forest, IL 60045.
ANDA 070562 .............................
Epirubicin Hydrochloride (HCl) Injection USP, 10 milligrams (mg)/5 milliliters (mL), 50 mg/25 mL, 150
mg/75 mL, and 200 mg/100 mL.
Flurazepam HCl Capsules USP, 15 mg .....................
ANDA 070563 .............................
ANDA 071808 .............................
Flurazepam HCl Capsules USP, 30 mg .....................
Flurazepam HCl Capsules USP, 15 mg .....................
ANDA 071809 .............................
ANDA 076827 .............................
Flurazepam HCl Capsules USP, 30 mg .....................
Vinorelbine Injection USP, Equivalent to 10 mg base/
mL.
Polyethylene Glycol 3350 Powder for Oral Solution,
17 grams/scoopful.
ANDA 077736 .............................
ANDA 085763 .............................
Glutethimide Tablets, 500 mg .....................................
ANDA 085791 .............................
ANDA 087297 .............................
Pentobarbital Sodium Capsules, 100 mg ....................
Glutethimide Tablets, 500 mg .....................................
ANDA 088819 .............................
Aristocort A (triamcinolone acetonide) Cream, 0.1% ..
ANDA 089459 .............................
Glutethimide Tablets, 500 mg .....................................
VerDate Sep<11>2014
18:30 Feb 11, 2019
Jkt 247001
PO 00000
Frm 00057
Fmt 4703
Sfmt 4703
Pharmaceutical Basics, Inc., 301 South Cherokee
St., Denver, CO 80223.
Do.
Halsey Drug Co., Inc., 1827 Pacific St., Brooklyn, NY
11233.
Do.
Hospira, Inc.
Breckenridge Pharmaceutical, Inc., 6111 Broken
Sound Parkway NW, Suite 170, Boca Raton, FL
33487.
Chelsea Laboratories, Inc., 896 Orlando Ave., West
Hampstead, NY 11552.
Do.
Phoenix Pharmaceuticals, Inc., 111 Leuning St.,
South Hackensack, NJ 07606.
Astellas Pharma U.S., Inc., Three Parkway North,
Deerfield, IL 60015.
Halsey Drug Co., Inc.
E:\FR\FM\12FEN1.SGM
12FEN1
]]>Agencies
[Federal Register Volume 84, Number 29 (Tuesday, February 12, 2019)]
[Notices]
[Pages 3462-3467]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-01962]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2014-N-1721]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Investigational New
Drug Applications
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by March
14, 2019.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
Fax: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All
comments should be identified with the OMB control number 0910-0014.
Also include the FDA docket number found
[[Page 3463]]
in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: JonnaLynn Capezzuto, Office of
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-3794,
PRAStaff@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
Investigational New Drug Application--21 CFR Part 312
OMB Control Number 0910-0014-Extension
This information collection supports FDA regulations in 21 CFR part
312 covering Investigational New Drugs. Part 312 implements provisions
of section 505(i) of the Federal Food, Drug, and Cosmetic Act (FD&C
Act) (21 U.S.C. 355(i)) requiring FDA to issue regulations under which
the clinical investigation of the safety and effectiveness of
unapproved new drugs and biological products can be conducted.
FDA is charged with implementing statutory requirements that ensure
drug products marketed in the United States are shown to be safe and
effective, properly manufactured, and properly labeled for their
intended uses. Section 505(a) of the FD&C Act provides that a new drug
may not be introduced or delivered for introduction into interstate
commerce in the United States unless FDA has previously approved a new
drug application (NDA). FDA approves an NDA only if the sponsor of the
application first demonstrates that the drug is safe and effective for
the conditions prescribed, recommended, or suggested in the product's
labeling. Proof must consist, in part, of adequate and well-controlled
studies, including studies in humans, that are conducted by qualified
experts.
The investigational new drug application (IND) regulations under
part 312 establish reporting requirements that include an initial
application as well as amendments to that application, reports on
significant revisions of clinical investigation plans, and information
on a drug's safety or effectiveness. In addition, the sponsor is
required to give FDA an annual summary of the previous year's clinical
experience. The regulations also include recordkeeping requirements
pertaining to the disposition of drugs, records pertaining to
individual case histories, and certain other documentation verifying
the fulfillment of responsibilities by clinical investigators.
Submissions are reviewed by medical officers and other Agency
scientific reviewers assigned responsibility for overseeing a specific
study. The details and complexity of these requirements are dictated by
the scientific procedures and human subject safeguards that must be
followed in the clinical tests of investigational new drugs.
The IND information collection requirements provide the means by
which FDA can monitor the clinical investigation of the safety and
effectiveness of unapproved new drugs and biological products,
including the following: (1) Monitor the safety of ongoing clinical
investigations; (2) determine whether the clinical testing of a drug
should be authorized; (3) ensure production of reliable data on the
metabolism and pharmacological action of the drug in humans; (4) obtain
timely information on adverse reactions to the drug; (5) obtain
information on side effects associated with increasing doses; (6)
obtain information on the drug's effectiveness; (7) ensure the design
of well-controlled, scientifically valid studies; and (8) obtain other
information pertinent to determining whether clinical testing should be
continued and information related to the protection of human subjects.
Without the information provided by industry as required under the IND
regulations, FDA cannot authorize or monitor the clinical
investigations that must be conducted before authorizing the sale and
general use of new drugs. These reports enable FDA to monitor a study's
progress, to ensure the safety of subjects, to ensure that a study will
be conducted ethically, and to increase the likelihood that the sponsor
will conduct studies that will be useful in determining whether the
drug should be marketed and available for use in medical practice.
To assist respondents with certain reporting requirements under
part 312, we have developed two forms: Form FDA 1571 entitled,
``Investigational New Drug Application (IND)'' and Form FDA 1572
entitled, ``Statement of Investigator.'' Anyone who intends to conduct
a clinical investigation must submit Form FDA 1571 as instructed. The
reporting elements include: (1) A cover sheet containing background
information on the sponsor and investigator; (2) a table of contents;
(3) an introductory statement and general investigational plan; (4) an
investigator's brochure describing the drug substance; (5) a protocol
for each planned study; (6) chemistry, manufacturing, and control
information for each investigation; (7) pharmacology and toxicology
information for each investigation; and (8) previous human experience
with the investigational drug. Form FDA 1572 is executed and submitted
by the IND sponsor before an investigator may participate in an
investigation. It includes background information on the investigator
as well as the investigation, and a general outline of the planned
investigation and study protocol.
In the Federal Register of October 4, 2018 (83 FR 50102) FDA
published a 60-day notice requesting public comment on the proposed
collection of information. We received one comment. The comment did not
pertain to the regulations or estimates provided in the 60-day notice
requesting that OMB extend its approval for the information collection
in these regulations. Rather, the comment discussed issues that
pertained to Docket No. FDA-2010-D-0503 for the ``Guidance for Clinical
Investigators, Sponsors, and Institutional Review Boards (IRBs):
Investigational New Drug Applications (INDs)--Determining Whether Human
Research Studies Can Be Conducted Without an IND.'' Accordingly, we
have submitted the comment to Docket No. FDA-2010-D-0503.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden for Human Drugs (CDER) \1\
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
----------------------------------------------------------------------------------------------------------------
Sec. 312.2(e); Requests for 400 1 400 24 9,600
FDA advice on the applicability
of part 312 to a planned
clinical investigation.........
Sec. 312.8; Requests to charge 74 1.23 91 48 4,368
for an investigational drug....
Sec. 312.10; Requests to waive 86 1.84 158 24 3,792
a requirement in part 312......
[[Page 3464]]
Sec. 312.23(a) through (f); 2,187 1.7 3,718 1,600 5,948,800
IND content and format
(including Form FDA 1571)......
Sec. 312.30(a) through (e); 4,418 5.52 24,387 284 6,925,908
Protocol amendments............
Sec. 312.31(b); Information 6,691 3.32 22,214 100 2,221,400
amendments.....................
Sec. 312.32(c) and (d); IND 867 15.78 13,681 32 437,792
safety reports.................
Sec. 312.33(a) through (f); 3,376 2.86 9,655 360 3,475,800
IND annual reports.............
Sec. 312.38(b) and (c); 930 1.61 1,497 28 41,916
Notifications of withdrawal of
an IND.........................
Sec. 312.42; Sponsor requests 198 1.38 273 284 77,532
that a clinical hold be
removed, including sponsor
submission of a complete
response to the issues
identified in the clinical hold
order..........................
Sec. 312.44(c) and (d); 12 1.16 14 16 224
Sponsor responses to FDA when
IND is terminated..............
Sec. 312.45(a) and (b); 231 1.84 425 12 5,100
Sponsor requests for or
responses to an inactive status
determination of an IND by FDA.
Sec. 312.47; Meetings, 122 1.51 184 160 29,440
including ``End-of-Phase 2''
meetings and ``Pre-NDA''
meetings.......................
Sec. 312.54(a); Sponsor 15 2.4 36 48 1,728
submissions to FDA concerning
investigations involving an
exception from informed consent
under Sec. 50.24.............
Sec. 312.54(b); Sponsor 2 1 2 48 96
notifications to FDA and others
concerning an IRB determination
that it cannot approve research
because it does not meet the
criteria in the exception from
informed consent in Sec.
50.24(a).......................
Sec. 312.56(b), (c), and (d); 6,100 7 42,700 80 3,416,000
Sponsor notifications to FDA
and others resulting from: (1)
The sponsor's monitoring of all
clinical investigations and
determining that an
investigator is not in
compliance with the
investigation agreements; (2)
the sponsor's review and
evaluation of the evidence
relating to the safety and
effectiveness of the
investigational drug; and (3)
the sponsor's determination
that the investigational drug
presents an unreasonable and
significant risk to subjects...
Sec. 312.58(a); Sponsor's 73 1 73 8 584
submissions of clinical
investigation records to FDA on
request during FDA inspections.
Sec. 312.70; During the 4 1 4 40 160
disqualification process of a
clinical investigator by FDA,
the number of investigator
responses or requests to FDA
following FDA's notification to
an investigator of its failure
to comply with investigation
requirements...................
Sec. 312.110(b)(4) and (b)(5); 11 26.28 289 75 21,675
Written certifications and
written statements submitted to
FDA relating to the export of
an investigational drug........
Sec. 312.120(b); Submissions 1,414 8.62 12,189 32 390,048
to FDA of ``supporting
information'' related to the
use of foreign clinical studies
not conducted under an IND.....
Sec. 312.120(c); Waiver 35 2.34 82 24 1,968
requests submitted to FDA
related to the use of foreign
clinical studies not conducted
under an IND...................
Sec. 312.130; Requests for 3 1 3 8 24
disclosable information in an
IND and for investigations
involving an exception from
informed consent under Sec.
50.24..........................
Sec. Sec. 312.310(b) and 935 2.77 2,590 8 20,720
312.305(b); Submissions related
to expanded access and
treatment of an individual
patient........................
Sec. 312.310(d); Submissions 480 2.15 1,032 16 16,512
related to emergency use of an
investigational new drug.......
Sec. Sec. 312.315(c) and 118 2.52 297 120 35,640
312.305(b); Submissions related
to expanded access and
treatment of an intermediate-
size patient population........
Sec. 312.320(b); Submissions 10 12.9 129 300 38,700
related to a treatment IND or
treatment protocol.............
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 23,125,527
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
[[Page 3465]]
Table 2--Estimated Annual Recordkeeping Burden for Human Drugs (CDER) \1\
----------------------------------------------------------------------------------------------------------------
Number of Average burden
21 CFR section Number of records per Total annual per Total hours
recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
Sec. 312.52(a); Sponsor 1,300 1 1,300 2 2,600
records for the transfer of
obligations to a contract
research organization..........
Sec. 312.57; Sponsor 13,000 1 13,000 100 1,300,000
recordkeeping showing the
receipt, shipment, or other
disposition of the
investigational drug and any
financial interests............
Sec. 312.62(a); Investigator 13,000 1 13,000 40 520,000
recordkeeping of the
disposition of drugs...........
Sec. 312.62(b); Investigator 13,000 1 13,000 40 520,000
recordkeeping of case histories
of individuals.................
Sec. 312.160(a)(3); Records 547 1.43 782 * 0.50 391
pertaining to the shipment of
drugs for investigational use
in laboratory research animals
or in vitro tests..............
Sec. 312.160(c); Shipper 547 1.43 782 * 0.50 391
records of alternative
disposition of unused drugs....
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 2,343,382
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
* 30 minutes.
Table 3--Estimated Annual Third-Party Disclosure Burden for Human Drugs (CDER) \1\
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of disclosures Total annual Average burden Total hours
respondents per respondent disclosures per disclosure
----------------------------------------------------------------------------------------------------------------
Sec. 312.53(c); Investigator 1,732 7.94 13,752 80 1,100,160
reports submitted to the
sponsor, including Form FDA
1572, curriculum vitae,
clinical protocol, and
financial disclosure...........
Sec. 312.55(a); Investigator 995 4 3,980 48 191,040
brochures submitted by the
sponsor to each investigator...
Sec. 312.55(b); Sponsor 995 4 3,980 48 191,040
reports to investigators on new
observations, especially
adverse reactions and safe use.
Sec. 312.64; Investigator 13,000 1 13,000 24 312,000
reports to the sponsor,
including progress reports,
safety reports, final reports,
and financial disclosure
reports........................
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 1,794,240
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 4--Estimated Annual Reporting Burden for Biologics (CBER) \1\
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
----------------------------------------------------------------------------------------------------------------
Sec. 312.2(e); Requests for 217 1.18 256 24 6,144
FDA advice on the applicability
of part 312 to a planned
clinical investigation.........
Sec. 312.8; Requests to charge 20 1.50 30 48 1,440
for an investigational drug....
Sec. 312.10;Requests to waive 2 1 2 24 48
a requirement in part 312......
Sec. 312.23(a) through (f); 335 1.35 452 1,600 723,200
IND content and format.........
Sec. 312.30(a) through (e); 694 5.84 4,053 284 1,151,052
Protocol amendments............
Sec. 312.31 (b); Information 77 2.43 187 100 18,700
amendments.....................
Sec. 312.32(c) and (d); IND 161 8.83 1,422 32 45,504
Safety reports.................
Sec. 312.33(a) through (f); 745 2.14 1,594 360 573,840
IND Annual reports.............
Sec. 312.38(b) and (c); 134 1.69 226 28 6,328
Notifications of withdrawal of
an IND.........................
Sec. 312.42; Sponsor requests 67 1.30 87 284 24,708
that a clinical hold be
removed, including sponsor
submission of a complete
response to the issues
identified in the clinical hold
order..........................
Sec. 312.44(c) and (d); 34 1.15 39 16 624
Sponsor responses to FDA when
IND is terminated..............
Sec. 312.45(a) and (b); 55 1.38 76 12 912
Sponsor requests for or
responses to an inactive status
determination of an IND by FDA.
Sec. 312.47; Meetings, 88 1.75 154 160 24,640
including ``End-of-Phase 2''
meetings and ``Pre-NDA''
meetings.......................
Sec. 312.53(c); Investigator 453 6.33 2,867 80 229,360
reports submitted to the
sponsor, including Form FDA
1572, curriculum vitae,
clinical protocol, and
financial disclosure...........
[[Page 3466]]
Sec. 312.54(a); Sponsor 1 1 1 48 48
submissions to FDA concerning
investigations involving an
exception from informed consent
under Sec. 50.24.............
Sec. 312.54(b); Sponsor 1 1 1 48 48
notifications to FDA and others
concerning an IRB determination
that it cannot approve research
because it does not meet the
criteria in the exception from
informed consent in Sec.
50.24(a).......................
Sec. 312.55(a); Number of 239 1.91 456 48 21,888
investigator brochures
submitted by the sponsor to
each investigator..............
Sec. 312.55(b); Number of 243 4.95 1,203 48 57,744
sponsor reports to
investigators on new
observations, especially
adverse reactions and safe use.
Sec. 312.56(b), (c), and (d); 108 2.21 239 80 19,120
Sponsor notifications to FDA
and others resulting from: (1)
The sponsor's monitoring of all
clinical investigations and
determining that an
investigator is not in
compliance with the
investigation agreements; (2)
the sponsor's review and
evaluation of the evidence
relating to the safety and
effectiveness of the
investigational drug; and (3)
the sponsor's determination
that the investigational drug
presents an unreasonable and
significant risk to subjects...
Sec. 312.58(a); Number of 7 1 7 8 56
sponsor's submissions of
clinical investigation records
to FDA on request during FDA
inspections....................
Sec. 312.64; Number of 2,728 3.82 10,421 24 250,104
investigator reports to the
sponsor, including progress
reports, safety reports, final
reports, and financial
disclosure reports.............
Sec. 312.70; During the 5 1 5 40 200
disqualification process of a
clinical investigator by FDA,
the number of investigator
responses or requests to FDA
following FDA's notification to
an investigator of its failure
to comply with investigation
requirements...................
Sec. 312.110(b)(4) and (b)(5); 18 1 18 75 1,350
Number of written
certifications and written
statements submitted to FDA
relating to the export of an
investigational drug...........
Sec. 312.120(b); Number of 280 9.82 2,750 32 88,000
submissions to FDA of
``supporting information''
related to the use of foreign
clinical studies not conducted
under an IND...................
Sec. 312.120(c); Number of 7 2.29 16 24 384
waiver requests submitted to
FDA related to the use of
foreign clinical studies not
conducted under an IND.........
Sec. 312.130; Number of 350 1.34 469 8 3,752
requests for disclosable
information in an IND and for
investigations involving an
exception from informed consent
under Sec. 50.24.............
Sec. 312.310(b) and 78 1.08 84 8 672
312.305(b); Number of
submissions related to expanded
access and treatment of an
individual patient.............
Sec. 312.310(d);Number of 76 2.76 210 16 3,360
submissions related to
emergency use of an
investigational new drug.......
Sec. 312.315(c) and 9 1 9 120 1,080
312.305(b); Number of
submissions related to expanded
access and treatment of an
intermediate-size patient
population.....................
Sec. 312.320(b); Number of 1 1 1 300 300
submissions related to a
treatment IND or treatment
protocol.......................
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 3,254,606
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 5--Estimated Annual Recordkeeping Burden for Biologics (CBER) \1\
----------------------------------------------------------------------------------------------------------------
Number of Average burden
21 CFR section Number of records per Total annual per Total hours
recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
Sec. 312.52(a); Sponsor 75 1.40 105 2 210
records for the transfer of
obligations to a contract
research organization..........
Sec. 312.57; Sponsor 335 2.70 904 100 90,400
recordkeeping showing the
receipt, shipment, or other
disposition of the
investigational drug, and any
financial interests............
[[Page 3467]]
Sec. 312.62(a); Investigator 453 1 453 40 18,120
recordkeeping of the
disposition of drugs...........
Sec. 312.62(b); Investigator 453 1 453 40 18,120
recordkeeping of case histories
of individuals.................
Sec. 312.160(a)(3); Records 111 1.40 155 * 0.5 78
pertaining to the shipment of
drugs for investigational use
in laboratory research animals
or in vitro tests..............
Sec. 312.160(c); Shipper 111 1.40 155 * 0.5 78
records of alternative
disposition of unused drugs....
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 127,006
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
* 30 minutes.
Because we have received an increased number of IND submissions
since the last OMB approval of the information collection, we have
increased our estimate of the associated burden accordingly.
Dated: February 6, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-01962 Filed 2-11-19; 8:45 am]
BILLING CODE 4164-01-P
